Inhibition of HDAC activity directly reprograms murine embryonic stem cells to trophoblast stem cells

Embryonic stem cells (ESCs) can differentiate into all cell types of the embryonic germ layers. ESCs can also generate totipotent 2C-like cells and trophectodermal cells. However, these latter transitions occur at low frequency due to epigenetic barriers, the nature of which is not fully understood. Here, we show that treating mouse ESCs with sodium butyrate (NaB) increases the population of 2C-like cells and enables direct reprogramming of ESCs into trophoblast stem cells (TSCs) without a transition through a 2C-like state. Mechanistically, NaB inhibits histone deacetylase activities in the LSD1-HDAC1/2 corepressor complex. This increases acetylation levels in the regulatory regions of both 2C- and TSC-specific genes, promoting their expression. In addition, NaB-treated cells acquire the capacity to generate blastocyst-like structures that can develop beyond the implantation stage in vitro and form deciduae in vivo. These results identify how epigenetics restrict the totipotent and trophectoderm fate in mouse ESCs.</p

Facile Preparation of Wurtzite CuInE₂ (E = S, Se) Nanoparticles Under Solvothermal Conditions

In this work, the synthesis of nanoscale CuInS₂ and CuInSe₂ was developed using molecular precursors of the type [(Ph₃P)₂­CuIn­(ER)₄] (E = S, Se) and solvothermal reactions. Various conditions were investigated including the use of different precursors, reaction temperatures, reaction times and the addition of a secondary chalcogen source to mixtures. After optimizing conditions, nanoparticles of CuInS₂ and CuInSe₂ were isolated with controlled sizes in the range of 2–5 nm (wurtzite structure), which ultimately tuned the band gap energies of the materials. Characterization methods including powder X-ray diffraction, electron microscopy, and optical spectroscopy were used to investigate their structures and photophysical properties

An Efficient and Economical Combination of Exploration Methods for Pb-Zn Polymetallic Skarn Deposits: A Case Study of the Periphery of Hetaoping Deposit, Yunnan Province, China

The Hetaoping ore district in Baoshan City, Yunnan Province, is one of the major localities of Pb-Zn polymetallic skarn deposits in China, where geophysical and geochemical surveys play an important role in exploring Pb-Zn polymetallic mineral resources. Based on the exploration and prospecting carried out at the periphery of the Hetaoping Pb-Zn polymetallic deposit, this study proposed an aero-ground joint exploration method to determine the metallogenic model of distal skarns in the Hetaoping ore district, achieving ideal prospecting results. The steps of this method are as follows. First, the locations of ore-induced anomalies were determined using high-amplitude aeromagnetic anomalies. Then, the ore-induced anomalies were determined to be anomalies of Pb-Zn polymetallic deposits through geochemical surveys of soil samples and ground geophysical surveys. Based on these data, a quantitative analysis and metallogenic potential assessment of ore bodies and their surrounding rocks were conducted using the interactive 2.5D magnetic inversion. In addition, the 3D inversion of regional gravity data was also performed in order to determine the spatial location of the deep magma chamber. Accordingly, the metallogenic geological process in this area was analyzed by determining the spatial morphology of the deep magma chamber, and a prospecting model of the Pb-Zn polymetallic deposits was finally built. The results show that the aero-ground joint exploration method, which first conducts a rapid scanning survey using the aeromagnetic method and then locates, distinguishes, and assesses significant aeromagnetic anomalies by combining comprehensive verification means such as ground geophysical, geochemical, and geological surveys, is efficient and economical. This study will guide regional metallogenic research and the exploration and prospecting of Pb-Zn polymetallic deposits

Tunable release of ions from graphene oxide laminates for sustained antibacterial activity in a biomimetic environment

Silver has long been recognised for its potent antimicrobial properties, but achieving a slow and longer-term delivery of silver ions presents significant challenges. While several attempts have been made to achieve controlled dosages of silver ions, sustaining their release for more than a few days in a biomimetic environment, particularly in the presence of complex proteins, has not been successfully demonstrated. This challenge is underscored by the absence of technology for sustaining antimicrobial activity, especially in the context of orthopaedic implants where long‐term efficacy, extending beyond seven days, is essential. In this study, we have successfully demonstrated the tunable, slow, and longer-term release of silver ions from the two-dimensional nanocapillaries (1 nm wide) of GO laminates incorporated with Ag ions (Ag-GO) for antimicrobial applications. To closely mimic a physiologically relevant serum-basedenvironment, we introduce a novel in vitro study model using 100% fetal bovine serum (FBS) as the test medium for microbiology, biocompatibility, and bioactivity studies. To emulate fluid circulation in a physiological environment, we challenge our in vitro studies with serum exchange protocols on different days. Our findings show that the Ag-GO coating can sustainably release silver ions at a minimum dosage of 10 μg/cm2/day, providing an effective and sustained antimicrobial barrier for over ten days

Association between Blood Manganese Levels and Visceral Adipose Tissue in the United States: A Population-Based Study

Background: Manganese (Mn) is an essential trace element with a narrow toxic margin for human health. The association between Mn exposure and adverse visceral adipose tissue (VAT) accumulation is unclear. Objective: This study aimed to estimate the associations of blood Mn levels with VAT mass or visceral obesity in the general population in the United States. Method: This cross-sectional study included data of 7297 individuals released by National Health and Nutrition Examination Survey (NHANES). VAT was quantified with dual-energy X-ray absorptiometry, and blood Mn was measured using inductively coupled plasma mass spectrometry. The generalized linear model and generalized additive model (GAM) were applied to estimate the linear and non-linear associations between Mn levels and VAT mass, respectively. Logistic regression was used to estimate the associations between blood Mn levels and the risk of visceral obesity. Results: Fully adjusted generalized linear regression revealed that individuals in the higher quantile of Mn had increased VAT mass compared with those in the lower quantile (β per quantile change = 0.025; 95% CI of 0.017, 0.033; p p = 0.020); female: β per quantile change = 0.036; 95% CI of 0.023, 0.048 (p 1 in total participants, males, and females). A stratified analysis found significant interactions between Mn and the family income-to-poverty ratio (PIR) in males, with stronger associations in males with a PIR p < 0.001). Conclusions: Higher blood Mn levels were positively associated with increased VAT mass and visceral obesity risk. The adverse VAT phenotype associated with excessive blood Mn levels should be further investigated

Small-molecule induction of phospho-eIF4E sumoylation and degradation via targeting its phosphorylated serine 209 residue

As phospho-eIF4E (p-eIF4E), unlike total eIF4E (t-eIF4E) essential for normal cells, is specifically required by cancer cells, it is an attractive, yet unrealized, target for anti-tumor intervention. Here we identify a small molecule, homoharringtonine (HHT), that antagonizes p-eIF4E function and eradicates acute myeloid leukemia (AML) expressing high level of p-eIF4E in vitro and in vivo. HHT selectively reduces p-eIF4E levels of leukemia cells without affecting t-eIF4E. HHT targets the phosphorylated serine 209 residue of p-eIF4E and induces p-eIF4E oligomerization, which enhances its interaction with the small ubiquitin-like protein modifier (SUMO)-conjugating enzyme UBC9, resulting in proteasome-dependent degradation of p-eIF4E via SUMO2/3-mediated SUMOylation. These results suggest that the phosphorylated serine 209 residue of p-eIF4E might be a potential target for developing small molecule-based new therapies for leukemia